It's a Trap! CDK8 Inhibition Reveals a Shared Vulnerability through Mediator Trapping in Fusion-Driven Pediatric Sarcomas
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Updated: Nov 3, 2026

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
Published on: May 14, 2016
Bradley T Stevens1,2, Mark E Hatley1,2
1Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Abstract:
A large proportion of pediatric sarcomas are driven by neomorphic transcription factors that are challenging therapeutic targets. In this issue, two independent studies identify CDK8 as a shared therapeutic vulnerability in pediatric fusion oncoprotein-driven sarcomas and reveal that CDK8 inhibitors disrupt oncogenic transcriptional programs through an unexpected gain-of-function mechanism involving Mediator complex trapping on chromatin. See related article by Zhang et al., p. 2344 See related article by McGinnis et al., p. 2366.
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